a study comparing abemaciclib plus temozolomide to temozolomide monotherapy in children and young adults with high-grade glioma following radiotherapy

Conditions: Glioma

Summary: the purpose of this study is to measure the benefit of adding abemaciclib to the chemotherapy, temozolomide, for newly diagnosed high-grade glioma following radiotherapy. your participation could last approximately 11 months and possibly longer depending upon how you and your tumor respond.


Eligibility criteria:
inclusion criteria: * biopsy proven high-grade glioma (hgg) as defined by 2016 world health organization (who) classification criteria, grade 3-4 including: * anaplastic astrocytoma * anaplastic ganglioglioma * anaplastic oligodendroglioma. * anaplastic pleomorphic xanthoastrocytoma, * glioblastoma or as defined by the 2021 who classification criteria as molecularly characterized: * non-pontine diffuse midline glioma, h3 k27-altered, * diffuse hemispheric glioma, h3 g34-mutant * diffuse pediatric hgg, h3/idh-wildtype * infant-type hemispheric glioma * high-grade astrocytoma with piloid features * high-grade pleomorphic xanthoastrocytoma * idh-mutant diffuse glioma with homozygous cyclin- dependent kinase inhibitor 2a/b (cdkn2a/b) deletion, * idh-mutant and 1p/19q co-deleted oligodendroglioma * idh-mutant astrocytoma with homozygous cdkn2a/b deletion * contraceptive use should be consistent with local regulations for participants in clinical studies. * radiotherapy initiated within 6 weeks (+1 week) of diagnosis and administered over 6 weeks (±1 week). participants \<3 years of age, considered not suitable for radiotherapy may be eligible. * minimum of 4 weeks between completion of radiation and cycle 1 day 1 (c1d1). * maximum of 8 weeks between completion of radiation and c1d1. exceptional circumstances can be discussed with the medical monitor. * acute effects of prior therapies must be grade ≤1 unless deemed clinically insignificant by the investigator. * adequate hematologic and organ function ≤7 days prior to c1d1 * life expectancy of ≥8 weeks and deemed likely to complete at least 1 cycle of treatment. * a performance score of ≥60 using: 1. lansky scale for participants \<16 years 2. karnofsky scale for participants ≥16 years * able to swallow and/or have a gastric/nasogastric tube. * any current systemic steroid use dose must be stable or decreasing at least 7 days prior to c1d1. * able and willing to adhere to study procedures, including frequent blood draws and mri. * at least 28 days since any major surgery, laparoscopic procedure, or a significant traumatic injury. * has a body surface area (bsa) of ≥0.2 m2. exclusion criteria: participants are excluded if any of the following apply: * diffuse intrinsic pontine glioma (dipg) or diffuse midline glioma located in the pons. * recurrent or refractory hgg including any recurrence/progression during/after radiotherapy. * secondary hgg, defined as a previously treated low-grade glioma that now meets high- grade criteria, or that resulted from a previously treated malignancy. * have known pathogenic somatic mutations appropriate for an anaplastic lymphoma kinase (alk), b-rapidly accelerated fibrosarcoma (braf), or neurotrophic tyrosine receptor kinase (ntrk ) inhibitor, in regions where these therapies are available and deemed appropriate by the investigator. * prior hgg treatment (including bevacizumab), except for surgery and radiotherapy (with or without concomitant temozolomide). * current enrollment in another trial deemed incompatible with this study. * treatment with an investigational product within the last 30 days or 5 half-lives (whichever is longer). * prior malignancy within the previous 3 years that, per the investigator and the medical monitor, may affect interpretation of study results. * a preexisting medical condition(s) that, per the investigator, would preclude study participation. * any serious, active, systemic infection requiring iv antibiotic, antifungal, or antiviral therapy, including acute hepatitis b or c, or human immunodeficiency virus at c1d1. * intolerability or hypersensitivity such as urticaria, anaphylaxis, toxic necrolysis, and/or stevens-johnson syndrome to temozolomide, and/or abemaciclib, their excipients, or dacarbazine. * received a live virus vaccine within 28 days of c1d1. * pregnant, breastfeeding, or intend to become pregnant during the study.

Keywords: brain tumor central nervous system (cns) tumor spinal cord tumor cyclin-dependent kinase (cdk) 4/6 inhibitor